Atrial fibrillation is the most common abnormal heart rhythm affecting approximately 5.2 million people in United States, more than 10 million in China1,2 and 33 million world-wide.3 Despite improvements in primary and secondary prevention of coronary artery disease, and effective treatment of hypertension and other heart diseases, the prevalence of atrial fibrillation continues to rise. The rise in atrial fibrillation may, at least in part, be due to the longer average life span of humans. It is projected that atrial fibrillation prevalence will increase to 12.1 million cases in 2030 in the US.4 Atrial fibrillation predisposes patients, particularly elders, to a higher risk for stroke, heart failure, and death. About 35% of all strokes in the U.S. annually are attributed to atrial fibrillation.
One of the important treatment approaches for atrial fibrillation is to restore and maintain normal heart rhythm. Currently, there are two major clinical approaches for this treatment: (1) drug therapy; and (2) radiofrequency ablation. Both approaches have advantages and disadvantages, and both are insufficient to eliminate atrial fibrillation.
There is a higher reoccurrence rate of atrial fibrillation when patients are treated with drug therapy than radiofrequency ablation due to relatively poor efficacy and incidence of adverse effects of drugs for the management of atrial fibrillation. Although dofetilide has been used for the treatment of atrial fibrillation for more than 20 years,5,6 its annual prescription represents only 2% of antiarrhythmic drug prescription (versus another antiarrhythmic drug amiodarone that represents 45%) among only a few antiarrhythmic drugs available in the market.7 In addition, dofetilide has not been approved for use in Europe and China. The major reasons for insignificant use of dofetilide by clinicians include: its relatively suboptimal efficacy;8 a risk of QT prolongation leading to life-threatening ventricular arrhythmias termed torsade de points (TdP),9 as a result, a 3-day mandatory in-hospital loading period required by the US FDA; and the doctor who prescribes dofetilide and the hospital must have gone through special dofetilide training.
First line treatment approaches to TdP include removal of the offending causes and avoidance of QT-prolonging agents, such as treatment with dofetilide. It has been recently suggested that inhibition of the late sodium current (INa-L) may be an effective treatment approach to terminate TdP in acquired long QT syndromes (LQTS) specifically by dofetilide.10,11 
There remains a need for novel effective and safe methods and pharmaceutical compositions for treating or preventing atrial fibrillation and related symptoms. Specifically, there is a need for novel methods and pharmaceutical compositions that provide more effective prevention and/or treatment of atrial fibrillation in patients in need thereof, while reducing the risk of adverse effects, such as incidence of TdP. Such methods and pharmaceutical compositions are described in the present application.